1. The measurement of immunosuppressive drugs by mass spectrometry and immunoassay in a South African transplant setting
- Author
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Amy Strydom, Doreen Jacob, Taryn Pillay, Refeletse Malahlela, and Sean Currin
- Subjects
Immunoassay ,Immunosuppressants ,Mass spectrometry ,Therapeutic drug monitoring ,Medicine (General) ,R5-920 ,Chemistry ,QD1-999 - Abstract
Objectives: Liquid chromatography tandem mass spectrometry (LC-MS/MS) is the gold standard for measurement of immunosuppressive drugs (ISDs), but is technically demanding and less accessible in resource-limited countries. Immunoassays can also measure ISD concentrations, but may be limited by cross-reactivity. We evaluated the performance of the Roche electrochemiluminescence immunoassay (ECLIA) for cyclosporine, everolimus and sirolimus against LC-MS/MS in an African population for the first time. Methods: Bias for ECLIA was estimated by comparing ECLIA-measured ISD concentrations to those obtained by LC-MS/MS in 42, 43 and 47 patient samples for cyclosporine, everolimus and sirolimus, respectively. Precision was assessed by performing replicate measurements of quality control materials. Results: Deming regression analysis for all ISDs showed strong correlation between ECLIA and LC-MS/MS with a Pearson's r of >0.94. The slopes for cyclosporine, everolimus and sirolimus were 0.94 [95 % CI: 0.87–1.03], 1.35 [95 % CI: 1.23–1.44] and 0.96 [95 % CI: 0.85–1.15] with y-intercepts of 31.60 μg/L [95 % CI: 2.02–57.63], 0.23 μg/L [95 % CI: 0.21 – 0.72] and 2.61 μg/L [95 % CI: 1.30–3.56], respectively. Difference plots showed a median bias of 2.07 % [95 % CI: 1.42 – 6.99 %], 41.2 % [95 % CI: 34.9–51.8 %] and 34.9 % [95 % CI: 28.4–47.3 %] for cyclosporine, everolimus and sirolimus, respectively. Conclusions: The cyclosporine ECLIA yielded results comparable to LC-MS/MS while poorly comparable results were obtained for everolimus and sirolimus, which may be explained by ISD metabolite cross-reactivity, amongst other factors. The poor comparability, although not unique, is noteworthy and the clinical consequences of these differences require further investigation.
- Published
- 2024
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